5D90
Crystal structure of HiNmlR, a MerR family regulator lacking the sensor domain, bound to promoter DNA
Summary for 5D90
| Entry DOI | 10.2210/pdb5d90/pdb |
| Descriptor | MerR family regulator protein (2 entities in total) |
| Functional Keywords | merr family regulator, transcription |
| Biological source | Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) |
| Total number of polymer chains | 4 |
| Total formula weight | 62610.79 |
| Authors | Counago, R.M.,Chang, C.W.,Kobe, B. (deposition date: 2015-08-18, release date: 2016-06-29, Last modification date: 2016-08-31) |
| Primary citation | Counago, R.M.,Chen, N.H.,Chang, C.W.,Djoko, K.Y.,McEwan, A.G.,Kobe, B. Structural basis of thiol-based regulation of formaldehyde detoxification in H. influenzae by a MerR regulator with no sensor region. Nucleic Acids Res., 44:6981-6993, 2016 Cited by PubMed Abstract: Pathogenic bacteria such as Haemophilus influenzae, a major cause of lower respiratory tract diseases, must cope with a range of electrophiles generated in the host or by endogenous metabolism. Formaldehyde is one such compound that can irreversibly damage proteins and DNA through alkylation and cross-linking and interfere with redox homeostasis. Its detoxification operates under the control of HiNmlR, a protein from the MerR family that lacks a specific sensor region and does not bind metal ions. We demonstrate that HiNmlR is a thiol-dependent transcription factor that modulates H. influenzae response to formaldehyde, with two cysteine residues (Cys54 and Cys71) identified to be important for its response against a formaldehyde challenge. We obtained crystal structures of HiNmlR in both the DNA-free and two DNA-bound forms, which suggest that HiNmlR enhances target gene transcription by twisting of operator DNA sequences in a two-gene operon containing overlapping promoters. Our work provides the first structural insights into the mechanism of action of MerR regulators that lack sensor regions. PubMed: 27307602DOI: 10.1093/nar/gkw543 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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